This is a competing continuation application for renewal (Years #21-#25, 8/l/01-7/31/06) of a K05 Senior Scientist Award (SSA) held since 8/01/81. The overall objective of the research has been to investigate through epidemiological studies three major themes on substance use in adolescence and adulthood: developmental patterns of involvement and cessation in the use of various drugs; risk and protective factors for involvement in drugs; and consequences of using drugs. Stimulated by findings obtained in the current period of support, the goal for the next five years is to conduct a multifactorial examination of the development of nicotine dependence. Six specific aims will be pursued: (1) Describe the epidemiology and natural history of nicotine dependence and other aspects of smoking behavior, in particular the transition to daily smoking and nicotine dependence, among adolescents and young adults. (2) Identify psychological, social and biological factors that promote (risk factors) and factors that reduce the risk (protective factors) of daily smoking and the transition to nicotine dependence. (3) Specify the comorbidity of drug use and dependence with psychiatric symptoms among adolescents, in particular the sequencing and reciprocal relationships between nicotine dependence and depression. (4) Examine interpersonal influences on drug behavior, especially nicotine dependence, within and outside the family, and identify: a. the extent of familial similarity on drug behavior, including nicotine dependence, among parents and adolescents, siblings, and spouses; b. the relative contribution of genetic, shared and non-shared environmental factors to smoking onset, daily smoking and nicotine dependence among twins; c. the relative importance of selection and socialization on smoking among adolescent friendship pairs. (5) Identify pathways of progression in smoking, nicotine dependence, and the use of other drugs. (6) Identify gender and ethnic commonalities and differences for #1-#5. An overall goal is to incorporate a biological perspective in epidemiological research. Three interrelated research programs will be pursued to achieve these aims: analyses of a national longitudinal sample of young adults (Add Health), analyses of the National Household Surveys on Drug Abuse, and the implementation of a new longitudinal study of the transition to nicotine dependence in adolescence. The research will provide understanding crucial for the development of effective prevention and treatment interventions. Components of the program represent innovative activities in epidemiological research carried out on general population samples.